Expression Of Growth Factor Receptor Research Articles

The mechanism underlying metastasis in triple-negative breast cancer: focusing on the interplay between ferroptosis, epithelial-mesenchymal transition, and non-coding RNAs

Triple-negative breast cancer (TNBC) is a type of breast cancer with lack the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is the most aggressive breast cancer and the most difficult to treat due to its poor response to treatments and extremely invasive characteristics. The typical treatment for TNBC frequently results in relapse because of the lack of particular treatment choices. It is urgent to focus on identifying a workable and effective target for the treatment of TNBC. Cancer metastasis is significantly influenced by epithelial-mesenchymal transition (EMT). Ferroptosis is an iron-dependent cell death form, and changes its key factor to affect the proliferation and metastasis of TNBC. Several reports have established associations between EMT and ferroptosis in TNBC metastasis. Furthermore, non-coding RNA (ncRNA), which has been previously described, can also control cancer cell death and metastasis. Thus, in this review, we summarize the correlation and pathways among the ferroptosis, EMT, and ncRNAs in TNBC metastasis. Also, aim to find out a novel strategy for TNBC treatment through the ncRNA-ferroptosis-EMT axis.

Cordycepin and Its Structural Derivatives Effectively Suppress the High Expression of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase in Breast Carcinomas: A Computational Drug Development Approach.

Breast cancer is a frequently diagnosed malignant disease and the primary cause of mortality among women with cancer worldwide. The therapy options are influenced by the molecular subtype due to the intricate nature of the condition, which consists of various subtypes. By focusing on the activation of receptors, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase can be utilized as an effective drug target for therapeutic purposes of breast cancer. The objective of this study is to compare the underlying pharmacological properties of several modified agents to the parental Cordycepin to target and inhibit the EGFR tyrosine kinase high expression, and to discover the inhibitor with the highest affinity for this drug target to treat the breast cancer patients. The Maestro Application of Schrödinger Suite Paid Software was initially employed for conducting extra precision (XP) structure-based virtual screening to evaluate the binding affinity of the Cordycepin and its 500 structural derivatives with the EGFR tyrosine kinase protein structure. In addition, the anti-breast cancer activity of the chosen compounds was assessed by looking at their drug-likeness and ADMET characteristics using Lipinski's rule of five along with Quantitative structure- activity relationship (QSAR) validation, the prediction of cell line anti-cancer, as well as anti- breast cancer activity of top docked scored compounds. Subsequently, the Desmond paid software- based molecular dynamics simulations (MDS) were conducted for a duration of 100 nanoseconds on the promising candidates followed by the binding free energy estimation was performed utilizing MM-GBSA analysis. To determine the stability of the protein-ligand complex, root-meansquare deviation (RMSD), root-mean-square fluctuation (RMSF), protein-ligand interactions, and other necessary parameters were evaluated from the 100 ns MDS Trajectory. Based on the overall analysis of our study, N (6)-octylamine adenosine (CID-194932) reported the optimum inhibitory potential against the EGFR tyrosine kinase protein, followed by Adenosine 5-monophosphate (CID-83862) and Cordycepin (CID-6303), which compared favorably to the control drug Vandetanib (CID-3081361). Consequently, these derivative compounds Cordycepin have the potential to be utilized as lead molecules in the development of highly effective and potent EGFR tyrosine kinase inhibitors for the treatment of breast cancer patients.

IL-22-mediated microRNA-124-3p/GRB2 axis regulates hyperproliferation and inflammatory response of keratinocytes in psoriasis.

Psoriasis is an inflammatory dermatosis that features overproliferation and inflammatory reaction of keratinocytes. A study reported that IL-22 is involved in the pathogenesis of psoriasis by mediating miR-124 to regulate the expression of fibroblast growth factor receptor 2 in keratinocytes. A microRNA may target multiple target genes. Therefore, we speculate that miR-124-3p may also target other downstream genes to affect IL -22-induced keratinocyte function. A possible target gene of miR-124-3p, growth factor receptor-bound protein 2 (GRB2), was screened by analyzing the target gene databases. GRB2 expression was elevated and miR-124-3p expression was decreased in psoriatic lesions compared to psoriatic adjacent normal skins and healthy controls. We performed the following cell experiments in the IL-22-stimulated HaCaT cell model. In keratinocytes transfected with the miR-124-3p mimics, GRB2 expression was significantly lower. We analyzed the regulation of keratinocyte proliferation by GRB2 and miR-124-3p. High levels of GRB2 promoted keratinocyte proliferation and expression of Ki67, PCNA, and K16, which were inhibited by low expression of GRB2. In addition, we found that the effect of GRB2 inhibitors on the proliferation and inflammatory response of keratinocytes was dose-dependent. Finally, we investigated the influence of GRB2 on inflammatory mediators in keratinocytes with the ELISA. After low expression of GRB2, the mRNA expression and secretion of the pro-inflammatory factor were suppressed. When both GRB2 and miR-124-3p were overexpressed, the cellular overproliferation and inflammation caused by GRB2 overexpression were significantly reversed by miR-124-3p. In summary, IL-22-mediated miR-124-3p regulates keratinocyte hyperproliferation and inflammatory response by suppressing GRB2 expression in psoriasis.

Advancements in understanding the role and mechanism of sirtuin family (SIRT1-7) in breast cancer management.

Breast cancer (BC) is the most prevalent type of cancer in women worldwide and it is classified into a few distinct molecular subtypes based on the expression of growth factor and hormone receptors. Though significant progress has been achieved in the search for novel medications through traditional and advanced approaches, still we need more efficacious and reliable treatment options to treat different types and stages of BC. Sirtuins (SIRT1-7) a class III histone deacetylase play a major role in combating various cancers including BC. Studies reveal thateach sirtuin has a unique and well-balanced biology, indicating that it regulates a variety of biological processes that result in the initiation, progression,and metastasis of BC. SIRT also plays a major role in numerous vital biological functions, including apoptosis, axonal protection, transcriptional silencing, DNA recombination and repair, fat mobilization, and aging. As per the current demand, we wish to outline the structural insights into sirtuin's catalytic site, substantial variations among all SIRT types, and their mechanism in BC management. Additionally, this review will focus on the application of SIRT modulators along with their clinical significance, hurdles, and future perspective to develop successful SIRT-based drug candidates to conquer the BC problem.

Immunohistochemical Localization of Epidermal Growth Factor Receptor in Rat Buccal Mucosa Treated with Fenugreek Leaf Oil

The lack of effective treatment for oral mucosal ulcers has motivated clinicians to search for other therapeutic techniques to improve oral ulcer healing. Applying fenugreek to an ulcer triggers the release of its anti-inflammatory components, that might reduce any superfluous inflammatory processes and accelerate wound healing. The aim of this study was to investigate the effect of fenugreek leaf oil on the ulcer associated with the expression of epidermal growth factor receptor (EGFR). A total of 24 adult male rats weighing between 350 and 450 grams and 4-6 months of age were used in this study. The experimental design included: the normal group (no ulcer), the control group (12 ulcers left without treatment to the right), and the study group (12 ulcers on the left side were healed using fenugreek oil). All rats were sacrificed on the 3rd and 7th days of the experimental study, healing durations, and biological samples were prepared for histological and immunohistochemistry analysis of EGFR. The current study exhibited that the EGFR expression increased in ulcer sites treated with fenugreek after 3 days of ulceration with significant differences in comparison with other groups. In conclusion, fenugreek oil was efficient in promoting ulcer healing by enhancing epithelization. Moreover, the positive localization of EGFR increased in the study groups treated with fenugreek oil indicating its potential activity in accelerating the healing process‎‎‎.

Amiloride sensitizes prostate cancer cells to the reversible tyrosine kinase inhibitor lapatinib by modulating Erbb3 subcellular localization

Neoadjuvant therapy (NAT) has been studied in clinically localized prostate cancer (PCa) to improve the outcomes from radical prostatectomy (RP) by ‘debulking’ of high-risk PCa; however, using androgen deprivation therapy (ADT) at this point risks castration resistant PCa (CRPC) clonal proliferation. Our goal is to identify alternative NAT that reduce hormone sensitive PCa (HSPC) without affecting androgen receptor (AR) transcriptional activity. PCa is associated with increased expression and activation of the epidermal growth factor receptor (EGFR) family, including HER2 and ErbB3. The FDA-approved HER2 inhibitor lapatinib has been tested in PCa but was ineffective due to continued activation of ErbB3. We now demonstrate that this is due to ErbB3 being localized to the nucleus in HSPC and thus protected from lapatinib which affect membrane localized HER2/ErbB3 dimers. Here, we show that the well-established, well-tolerated potassium-sparing diuretic amiloride hydrochloride dose dependently prevented ErbB3 nuclear localization via formation of plasma membrane localized HER2/ErbB3 dimers. This in turn allowed lapatinib inactivation of these dimers via inhibition of its target HER2, which dephosphorylated ERK1/2 and inhibited survival. Amiloride combined with lapatinib significantly increased apoptosis at relatively low doses of both drugs but did not affect AR transcriptional activity. Thus, our data indicate that a combination of amiloride and lapatinib could target HSPC tumors without problems associated with using ADT as NAT in HSPC.

Analysis of Estrogen Receptor Alpha (ERα) Expression and Epidermal Growth Factor Receptor (EGFR) Mutation and Their Relationship with Hormonal and Menstrual Factors in Women with Lung Adenocarcinoma

Lung cancer is the second most common cancer worldwide. The proportion of non-smoking women with lung cancer is higher than non-smoking men. Studies have found gender differences in estrogen receptor alpha expression and mutation in the human epidermal growth factor receptor in tumour tissue. The aim of the study is to analyze the expression of estrogen receptor alpha (ERα) and epidermal growth factor receptor (EGFR) in women with lung adenocarcinoma. The study is retrospective and includes 41 non-smoking women with lung adenocarcinoma. We studied the expression of ERα and EGFR mutations in tumour tissue and their relationship with the hormonal and menstrual factors. The positive expression of ERα in tumour tissue is 9.8%, and in these patients, the estradiol levels were many times higher. EGFR mutation expression is found in 26.8%. There is a correlation between the expression of the EGFR mutation and the time of menopause. The expression of ERα and EGFR in non-smoking women with lung adenocarcinoma is most likely related to the influence of sex hormones and menstrual factors.

Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.

Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated. In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation. Flow cytometry was used to characterize pericytes by their expression of platelet-derived growth factor receptor β, neuroglial antigen 2, cluster of differentiation 13-alanyl aminopeptidase, and antigen Kiel 67. Microvessels were isolated for gene expression profiling and invitro pericyte expansion. Immunofluorescence validated the cell culture model. Plasma-derived extracellular vesicles from hypertensive rodents were applied as a treatment to assess their effects on pericyte function and detailed metabolic assessments on enriched pericytes measured oxidative phosphorylation and glycolysis. Our results reveal a shift in platelet-derived growth factor receptor β+ pericytes toward increased neuroglial antigen 2 and cluster of differentiation 13-alanyl aminopeptidase coexpression, indicative of their critical role in vascular stabilization and inflammatory responses within the hypertensive milieu. Significant alterations were found within key pathways including angiogenesis, blood-brain barrier integrity, hypoxia, and inflammation. Circulating extracellular vesicles from hypertensive rodents distinctly influenced pericyte mitochondrial function, evidencing their dual role as carriers of disease pathology and potential therapeutic agents. Furthermore, a shift toward glycolytic metabolism in hypertensive pericytes was confirmed, coupled with ATP production dysregulation. Our findings demonstrate that cerebral pericytes undergo phenotypic and metabolic reprogramming in response to hypertension, with hypertensive-derived plasma-derived extracellular vesicles impairing their mitochondrial function. Importantly, plasma-derived extracellular vesicles from normotensive controls restore this function, suggesting their potential as both therapeutic agents and precision biomarkers for hypertensive vascular complications. Further investigation into plasma-derived extracellular vesicle cargo is essential to further explore their therapeutic potential in vascular health.

Combining Water-Soluble Porphyrin and Phthalocyanine Photosensitizers With Doxorubicin Improves the Efficacy of Chemo-Photodynamic Therapy Against DMBA-Induced Breast Carcinoma.

Breast cancer ranks as the second most widespread form of cancer globally. Currently, combination therapy is being actively employed in clinical practice to augment the efficiency of anticancer treatment. Hence, the objective of this study was to assess the therapeutic efficacy of a combination of femtosecond laser-based photodynamic therapy (PDT) utilizing two distinct photosensitizers (PSs), zinc phthalocyanine tetrasulfonate (ZnPcS4) and α,β,χ,δ porphyrin-Tetrakis (1-methylpyridinium-4-yl) p-Toluenesulfonate porphyrin (TMPyP) in conjunction with doxorubicin chemotherapeutic agent, on mammary carcinomas experimentally induced in female mice using 7,12-dimethylbenz[a] anthracene (DMBA). Our results showed the efficiency of the combined therapy for promoting tissue apoptosis and necrosis as evidenced by histopathological observations and the noticeable reduction of Bcl-2 and Ki-67 expression. Moreover, there was a reduction in serum levels of the carcinoma antigen CA15-3 and transforming growth factor beta (TGF-β). Co-treatment of doxorubicin with ZnPcS4-PDT or TMPyP-PDT or a combination of both resulted in a decrease in the expression of epidermal growth factor receptor (EGFR) and its downstream oncogenes NRAS, NF-κB, mTERT, and c-Myc, and an increase in the expression of the caspase-3 apoptotic gene. These results validate the therapeutic potential of combining doxorubicin with PDT, highlighting the potential of this co-treatment strategy as a promising alternative for enhancing existing anticancer approaches.

15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway.

Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization. By utilizing 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, colony formation, transwell assays, and enzyme linked immunosorbent assay (ELISA), we investigated how 15d-PGJ2 affects A549 cell viability, proliferation, apoptosis, and invasion, as well as levels of interleukin (IL)-4, IL-13, and IL-17. Human monocytic cell line THP-1 was induced into M2 macrophages using phorbol 12-myristate 13-acetate and IL-4/IL-13, followed by treatment with 15d-PGJ2. The study employed flow cytometry to observe the polarization of macrophages, quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify epidermal growth factor receptor (EGFR) expression, western blot for identifying expression of macrophage marker proteins, and examining EGFR/rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf) activation. In a coculture setup, CD8+ T cells were shown to have a proliferation capacity by carboxifluorescein diacetate succinimidyl ester (CFSE), a killing ability by lactate dehydrogenase, and an analysis of their interferon gamma and tumor necrosis factor alpha levels by ELISA. 15d-PGJ2 reduced invasion capacity and expression of inflammatory cytokines, lowered A549 cell viability in a dose-dependent way, and promoted apoptosis. 15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8+ T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.

FGF20 Secreted From Dermal Papilla Cells Regulate the Proliferation and Differentiation of Hair Follicle Stem Cells in Fine-Wool Sheep.

Wool traits determine the market value of fine-wool sheep, and wool fibre-breaking elongation (fibres can be stretched or elongated before they break) is one of the important wool traits. The interaction between hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) determines hair follicle development in fine wool sheep, thereby directly influencing wool traits. A genome-wide association study based on pre-sequencing data identified FGF20, which was significantly associated with wool fibre-breaking elongation. The study reveals that the regulatory mechanism of FGF20 secreted from DPCs affects the proliferation and differentiation of HFSCs through a co-culture system, to provide a new perspective for fine-wool sheep breeding. After knocking down FGF20 expression in DPCs, the results showed that the expression of fibroblast growth factor receptor 2 (FGFR2) and fibroblast growth factor receptor 3 (FGFR3) in DPCs and HFSCs was significantly decreased (p < 0.05), the number of EdU-positive cells and cell viability was significantly decreased (p < 0.01), and the apoptosis rate was significantly increased (p < 0.05). Meanwhile, the differentiation markers of SOX9, NOTCH1 and β-Catenin in HFSCs were also significantly reduced (p < 0.05). These findings indicate that FGF20-knockdown in DPCs of fine-wool sheep inhibits the proliferation and differentiation of HFSCs in the co-culture system, providing a theoretical basis for elucidating the regulatory mechanism of hair follicle self-renewal and differentiation of fine-wool sheep and providing a co-culture system for regenerative medicine.

Consumption of Endogenous Caspase-3 Activates Molecular Theranostic Nanoplatform against Inflammation-Induced Profibrotic Positive Feedback in Pulmonary Fibrosis.

The limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents a promising shortcut to reverse PF. Herein, a specific molecular nanotheranostic (Casp-GNMT), which is triggered by endogenous cysteinyl aspartate specific proteinase-3 (caspase-3), boosts antifibrotic efficacy through bioimaging synergistic with chemotherapy at molecular level, facilitating by ionizable lipid and reactive oxygen species sensitive lipid for precise and manageable therapy. The activation of molecular imaging probe (pCY-pairs) by consumption of endogenous caspase-3 initiates fluorescence resonance energy transfer-guided theranostic pattern, aiming to restore mitochondrial dysfunction-induced oxidative stress and inflammatory responses in alveolar epithelial cells II (AECs II). This process sequentially resists the expression of interleukin-1β and vascular endothelial growth factor receptor through combined with nintedanib, further suppressing abnormal injury of AECs II and persistent migration and proliferation of inflammatory cells. Especially, the homeostasis of injured AECs II diminishes excessive accumulation of transforming growth factor-β to restrain myofibroblasts proliferation and collagen deposition, thereby amplifying the possibility of reversing PF. This theranostic nanoplatform is proposed to provide a prompt and exact approach to enhance diagnostic authenticity and treating efficiency through harnessing endogenous indicator for PF reversal.

Mammographic parameters as predictors of molecular subtype of breast cancer: a prospective analysis

BackgroundThe prevalence of breast cancer is increasing globally and its early detection is the need of hour for giving the patient a long disease-free meaningful life. The latest management regimes depend upon the biological behavior of the breast cancer that itself relies upon expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her 2) neu status for its molecular subtyping.AimTo determine the predictive value of mammographic parameters in identifying the estrogen and progesterone hormone receptor status, human epidermal growth factor receptor 2 (Her 2) neu expression and molecular subtypes of breast cancer.MethodsA prospective observational study was conducted from January 2021 to September 2022 in a tertiary care institute. The study enrolled 51 females with histopathologically proven invasive breast carcinoma. The patients underwent digital mammography followed by tissue biopsy. Mammographic parameters were based on Breast Imaging-Reporting and Data System (BI-RADS) imaging features. The molecular subtypes of breast cancer were grouped into four subtypes based on St. Gallen International Expert Consensus Panel 2013. The mammographic features were then statistically correlated with molecular subtypes of breast cancer.ResultsLuminal type A was the most common molecular subtype in our study [ 17 (33.33%)] followed by triple negative type [10(19.61%)]. Tumors with non-circumscribed margins were predicted to be Luminal A or Luminal B subtype (p value < 0.02). Tumor with microcalcification was strongly predicted to be Her 2 subtype with a statistically significant association (p value < 0.001). Circumscribed tumors with absence of microcalcification were predicted to be triple-negative type of breast cancer.ConclusionsKey features in mammography were significantly associated with breast cancer molecular subtypes. Knowledge of such correlations could help clinicians stratify breast cancer patients according to their likely molecular subtypes, potentially enabling earlier, more effective treatment or aiding in therapeutic decisions in countries where immunohistochemical (IHC) hormone receptor and Her 2 testing is not readily available.

Synergistic inhibitory effect of atmospheric pressure plasma and berberine on non‑small cell lung cancer cells via inducing apoptosis.

Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article's primary goal is to investigate the effect of combination on NSCLC and its associated characterization. Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells. The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.

Discovery of a molecular glue for EGFR degradation.

Aberrant expression of epidermal growth factor receptor (EGFR) plays a critical role in the pathogenesis of various tumors, potentially representing a target for therapeutic intervention. Nonetheless, EGFR remains a challenging protein to target pharmacologically in triple-negative breast cancer (TNBC). An emerging approach to address the removal of such proteins is the application of molecular glue (MG) degraders. These compounds facilitate protein-protein interactions between a target protein and an E3-ubiquitin ligase, subsequently leading to protein degradation. Herein, we identified a new MG (CDDO-Me, C-28 methyl ester of 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oic acid), which orchestrated binding between EGFR and KEAP1 (an E3-ubiquitin ligase adapter), thereby initiating the ubiquitination and degradation of EGFR. CDDO-Me directly interacted with the tyrosine kinase (TK) domain of EGFR, resulting in its degradation via an autophagy-dependent lysosomal pathway. Knockdown of KEAP1 decreased the degradation of EGFR by reducing its K63-linked ubiquitination, leading to diminished EGFR colocalization in autophagosomes and lysosomes. Notably, CDDO-Me attenuates TNBC progression by accelerating EGFR degradation in cell-derived xenografts and patient-derived organoid models, highlighting its clinical application potential. Consequently, induction of EGFR degradation through MG degraders represents a viable therapeutic strategy for TNBC.

Role of Harmaline in Inhibiting c-Myc, Altering Molecular Typing, and Promoting Apoptosis in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks effective targeted, endocrine therapeutic agents and the development of novel agents is costly and time-consuming. The objective of this study was to identify pharmaceuticals and natural products utilized in clinical practice that have the potential to inhibit the expression of Cellular-myelocytomatosis oncogene (c-Myc), based on a review of the current literature. The aim was to assess the effect of the specified drugs on c-Myc expression in TNBC cells, determine the most potent inhibitor, and evaluate its impact on TNBC cell proliferation, invasive migration, and apoptosis, as well as the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) at both the gene and protein levels. Explore its potential for treatment or adjuvant therapy for triple-negative breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify gene and protein expression levels. Flow cytometry was employed to measure cell proliferation and apoptosis, while the Transwell assay was utilized to assess cell invasion and migration. Harmaline emerged as the strongest inhibitor, significantly decreasing the expression of c-Myc at both the gene and protein levels in TNBC cells. It also inhibited cell proliferation, invasion, and migration while promoting apoptosis in TNBC cells. Additionally, there was a varying increase in the expression of ER and PR genes and proteins. While the expression of the HER-2 gene was elevated, there was no significant change in HER-2 protein levels. Notably, the expression of the phosphorylated HER-2 protein increased. Harmaline was found to promote apoptosis and inhibit cell proliferation, invasion, and migration in TNBC cells by targeting the inhibition of c-Myc. It also induced the re-expression of the ER, PR, and HER-2 genes, as well as the ER and PR proteins.

Effect of BMP15 and GDF9 in the IVM medium on subsequent oocyte competence and embryo development of prepubertal goats.

Oocyte-secreted factors (OSFs), such as BMP15 and GDF9, are soluble paracrine factors that drive cumulus cell differentiation and function, sustaining oocyte competence acquisition and embryo development. This study aimed to assess the effect of BMP15 and GDF9 on IVM medium of prepubertal goat oocytes. COCs were in vitro matured in absence (control group) or presence of 100ng/mL of BMP15, GDF9, or both. To determine cumulus-oocyte communication, transzonal projections (TZP) density at 0h, 6h, 12h and 24h of IVM were evaluated. After IVM, mitochondrial activity, intracellular ROS and glutathione (GSH) levels, the epidermal growth factor receptor (EGFR) expression in oocytes and cumulus cells, and cumulus expansion were assessed. Blastocyst production and quality were evaluated after parthenogenetic activation (PA) and IVF. IVM supplementation with BMP15 increased the TZP density during the first 6h of culture. After IVM, BMP15 increased mitochondrial activity, EGFR expression in oocytes and cumulus cells, and cumulus expansion compared to control, but ROS and GSH levels were similar to control. BMP15 improved blastocyst production following PA (15.5% vs 6.3%) and the number of cells in the blastocyst inner cell mass. No differences were observed on blastocyst production or quality following IVF. IVM supplementation with GDF9 did not improve results from control group in any parameters studied. Additionally, GDF9 in combination with BMP15 only improved mitochondrial activity and cumulus expansion over control. In conclusion, IVM medium supplementation with BMP15 (100ng/ml) improves COCs quality parameters and PA-blastocyst production and quality of prepubertal goat oocytes. However, GDF9 (100ng/mL) did not have any beneficial effect in this study and was possibly antagonistic to BMP15.

GCC2 promotes non-small cell lung cancer progression by maintaining Golgi apparatus integrity and stimulating EGFR signaling pathways

Fundamental changes in intracellular processes, such as overactive growth signaling pathways, are common in carcinomas and are targets of many cancer therapeutics. GRIP and coiled-coil containing 2 (GCC2) is a trans-Golgi network (TGN) golgin maintaining Golgi apparatus structure and regulating vesicle transport. Here, we found an aberrant overexpression of GCC2 in non-small cell lung cancer (NSCLC) and conducted shRNA-mediated gene knockdown to investigate the role of GCC2 in NSCLC progression. shRNA-mediated GCC2 knockdown suppressed NSCLC cell growth, migration, stemness, and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. In addition, GCC2 knockdown suppressed cancer cell exosome secretion and the oncogenic capacity of cancer cell-derived exosomes. Mechanistically, GCC2 inhibition decreased epidermal growth factor receptor (EGFR) expression and downstream growth and proliferation signaling. Furthermore, GCC2 inhibition compromised Golgi structural integrity in cancer cells, indicating a functional role of GCC2 in regulating intracellular trafficking and signaling to promote lung cancer progression. Together, these findings suggest GCC2 as a potential therapeutic target for the treatment of NSCLC.

Machine learning based ultrasomics noninvasive predicting EGFR expression status in hepatocellular carcinoma patients.

To investigate the ability of ultrasomics to noninvasively predict epidermal growth factor receptor (EGFR) expression status in patients with hepatocellular carcinoma (HCC). 198 HCC patients were comprised in the study (n = 138 in the training dataset and n = 60 in the test dataset). EGFR expression was detected by immunohistochemistry. Ultrasomics features from gray-scale ultrasound images were extracted. Intra-class correlation coefficient (ICC) screening, variance filtering, mutual information method, and extreme gradient boosting (XGboost) embedding method were applied for selecting the best features. Random forest (RF), XGBoost, support vector machine (SVM), decision tree (DT), and logistic regression (LR) 5 machine learning algorithms were used to construct clinical models, ultrasomics models, and clinical-ultrasomics combined models, respectively. Area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, decision curve analysis (DCA), and calibration curve were used to assess the predictive performance of the model. In 198 patients, high EGFR expression was observed in 100 patients and low EGFR expression was observed in 98 patients. The RF machine learning ultrasomics model was found to perform well, with the AUC of the training and test dataset being 0.929 (95%CI, 0.874-0.966) and 0.807 (95%CI, 0.684-0.897) respectively, the sensitivity being 0.843 and 0.767 respectively, the specificity being 0.857 and 0.800 respectively, and the accuracy being 0.850 and 0.783, respectively. The predictive performance of the combined model established by integrating ultrasomics features and clinical baseline characteristics was improved, with the AUC, sensitivity, specificity, and accuracy of the RF machine learning combined model for the training and test dataset reaching 0.937 (95%CI, 0.884-0.971), 0.822 (95%CI, 0.702-0.909); 0.857, 0.833; 0.857, 0.800; 0.857, 0.817, respectively. To predict the status of EGFR expression in HCC patients, the ultrasomics model and combined model created by five machine learning algorithms can be utilized as efficient and noninvasive techniques, and the ultrasomics model and combined model established by RF classifier have the best predictive performance.

Survival outcomes for HER2-low breast cancer: Danish national data.

We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification. Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI). 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status. HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity.